Absence of evidence to diagnose lectin pathway deficiencies with a monogenic inborn error of immunity

Abstract

The lectin pathway (LP) is the most ancient, and the most recently discovered, pathway of complement activation (Fig 1).1,2 The first genetic etiology of LP deficiency, namely, mannose-binding lectin (MBL), was described in 1991.3,4 Common deficiencies of MBL-associated serine protease 2 (MASP-2) and ficolin-3 were reported in the following years (Fig 1),1,5 opening the door of hope for precise diagnosis of at least some patients with suspected inborn errors of immunity (IEIs). However, subsequent work called into question the clinical significance of LP deficiencies.3,5 Case-control studies analyzing disease associations of gene variants of components of the LP have been the topic of numerous publica-tions.1 Herein, we discuss the evidence for considering whether deficiencies of the LP are IEIs with an associated clinical phenotype.